Quantitative Insights Into β-Lactamase Inhibitor’s Contribution in the Treatment of Carbapenemase-Producing Organisms With β-Lactams

Objectives: Carbapenemase-producing organisms (CPOs) are associated with high mortality rates. The recent development of β-lactamase inhibitors (BLIs) has made it possible to control CPO infections safely and effectively with β-lactams (BLs). This study aims to explicate the quantitative relationshi...

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Autores principales:	Yanfang Feng, Arend L. de Vos, Shakir Khan, Mary St. John, Tayyaba Hasan
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	carbapenemase β-lactamase inhibitor antimicrobial stewardship β-lactam antibiotics carbapenem resistance Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ced9a8f2ba2540d6b01b78ee9d7e353c
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spelling	oai:doaj.org-article:ced9a8f2ba2540d6b01b78ee9d7e353c2021-11-18T06:52:35ZQuantitative Insights Into β-Lactamase Inhibitor’s Contribution in the Treatment of Carbapenemase-Producing Organisms With β-Lactams1664-302X10.3389/fmicb.2021.756410https://doaj.org/article/ced9a8f2ba2540d6b01b78ee9d7e353c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.756410/fullhttps://doaj.org/toc/1664-302XObjectives: Carbapenemase-producing organisms (CPOs) are associated with high mortality rates. The recent development of β-lactamase inhibitors (BLIs) has made it possible to control CPO infections safely and effectively with β-lactams (BLs). This study aims to explicate the quantitative relationship between BLI’s β-lactamase inhibition and CPO’s BL susceptibility restoration, thereby providing the infectious disease society practical scientific grounds for regulating the use of BL/BLI in CPO infection treatment.Methods: A diverse collection of human CPO infection isolates was challenged by three structurally representative BLIs available in the clinic. The resultant β-lactamase inhibition, BL susceptibility restoration, and their correlation were followed quantitatively for each isolate by coupling FIBA (fluorescence identification of β-lactamase activity) and BL antibiotic susceptibility testing.Results: The β-lactamase inhibition and BL susceptibility restoration are positively correlated among CPOs under the treatment of BLIs. Both of them are dependent on the target CPO’s carbapenemase molecular identity. Of note, without sufficient β-lactamase inhibition, CPO’s BL susceptibility restoration is universally low across all tested carbapenemase molecular groups. However, a high degree of β-lactamase inhibition would not necessarily lead to a substantial BL susceptibility restoration in CPO probably due to the existence of non-β-lactamase BL resistance mechanisms.Conclusion: BL/BLI choice and dosing should be guided by quantitative tools that can evaluate the inhibition across the entire β-lactamase background of the CPO upon the BLI administion. Furthermore, rapid molecular diagnostics for BL/BLI resistances, especially those sensitive to β-lactamase independent BL resistance mechanisms, should be exploited to prevent ineffective BL/BLI treatment.Yanfang FengArend L. de VosArend L. de VosShakir KhanShakir KhanMary St. JohnMary St. JohnTayyaba HasanTayyaba HasanFrontiers Media S.A.articlecarbapenemaseβ-lactamase inhibitorantimicrobial stewardshipβ-lactam antibioticscarbapenem resistanceMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	carbapenemase β-lactamase inhibitor antimicrobial stewardship β-lactam antibiotics carbapenem resistance Microbiology QR1-502
spellingShingle	carbapenemase β-lactamase inhibitor antimicrobial stewardship β-lactam antibiotics carbapenem resistance Microbiology QR1-502 Yanfang Feng Arend L. de Vos Arend L. de Vos Shakir Khan Shakir Khan Mary St. John Mary St. John Tayyaba Hasan Tayyaba Hasan Quantitative Insights Into β-Lactamase Inhibitor’s Contribution in the Treatment of Carbapenemase-Producing Organisms With β-Lactams
description	Objectives: Carbapenemase-producing organisms (CPOs) are associated with high mortality rates. The recent development of β-lactamase inhibitors (BLIs) has made it possible to control CPO infections safely and effectively with β-lactams (BLs). This study aims to explicate the quantitative relationship between BLI’s β-lactamase inhibition and CPO’s BL susceptibility restoration, thereby providing the infectious disease society practical scientific grounds for regulating the use of BL/BLI in CPO infection treatment.Methods: A diverse collection of human CPO infection isolates was challenged by three structurally representative BLIs available in the clinic. The resultant β-lactamase inhibition, BL susceptibility restoration, and their correlation were followed quantitatively for each isolate by coupling FIBA (fluorescence identification of β-lactamase activity) and BL antibiotic susceptibility testing.Results: The β-lactamase inhibition and BL susceptibility restoration are positively correlated among CPOs under the treatment of BLIs. Both of them are dependent on the target CPO’s carbapenemase molecular identity. Of note, without sufficient β-lactamase inhibition, CPO’s BL susceptibility restoration is universally low across all tested carbapenemase molecular groups. However, a high degree of β-lactamase inhibition would not necessarily lead to a substantial BL susceptibility restoration in CPO probably due to the existence of non-β-lactamase BL resistance mechanisms.Conclusion: BL/BLI choice and dosing should be guided by quantitative tools that can evaluate the inhibition across the entire β-lactamase background of the CPO upon the BLI administion. Furthermore, rapid molecular diagnostics for BL/BLI resistances, especially those sensitive to β-lactamase independent BL resistance mechanisms, should be exploited to prevent ineffective BL/BLI treatment.
format	article
author	Yanfang Feng Arend L. de Vos Arend L. de Vos Shakir Khan Shakir Khan Mary St. John Mary St. John Tayyaba Hasan Tayyaba Hasan
author_facet	Yanfang Feng Arend L. de Vos Arend L. de Vos Shakir Khan Shakir Khan Mary St. John Mary St. John Tayyaba Hasan Tayyaba Hasan
author_sort	Yanfang Feng
title	Quantitative Insights Into β-Lactamase Inhibitor’s Contribution in the Treatment of Carbapenemase-Producing Organisms With β-Lactams
title_short	Quantitative Insights Into β-Lactamase Inhibitor’s Contribution in the Treatment of Carbapenemase-Producing Organisms With β-Lactams
title_full	Quantitative Insights Into β-Lactamase Inhibitor’s Contribution in the Treatment of Carbapenemase-Producing Organisms With β-Lactams
title_fullStr	Quantitative Insights Into β-Lactamase Inhibitor’s Contribution in the Treatment of Carbapenemase-Producing Organisms With β-Lactams
title_full_unstemmed	Quantitative Insights Into β-Lactamase Inhibitor’s Contribution in the Treatment of Carbapenemase-Producing Organisms With β-Lactams
title_sort	quantitative insights into β-lactamase inhibitor’s contribution in the treatment of carbapenemase-producing organisms with β-lactams
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/ced9a8f2ba2540d6b01b78ee9d7e353c
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Quantitative Insights Into β-Lactamase Inhibitor’s Contribution in the Treatment of Carbapenemase-Producing Organisms With β-Lactams

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